Research Paper

Clinical & Experimental Metastasis

, Volume 26, Issue 2, pp 153-159

Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo

  • Sumanta GoswamiAffiliated withDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva UniversityDepartment of Biology, Yeshiva University Email author 
  • , Ulrike PhilipparAffiliated withKoch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of TechnologyMerck Research Laboratories
  • , Daqian SunAffiliated withDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University
  • , Antonia PatsialouAffiliated withDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University
  • , Jacob AvrahamAffiliated withDepartment of Biology, Yeshiva University
  • , Weigang WangAffiliated withDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva UniversityImClone Systems Incorporated
  • , Francesca Di ModugnoAffiliated withLaboratory of Experimental Chemotherapy, Regina Elena Cancer Institute
  • , Paola NisticoAffiliated withLaboratory of Immunology, Regina Elena Cancer Institute
  • , Frank B. GertlerAffiliated withKoch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology
    • , John S. CondeelisAffiliated withDepartment of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University

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Abstract

We have studied the gene expression pattern of invasive primary mammary tumor cells using a unique in vivo invasion assay that isolates the invasive tumor cells by chemotaxis. One of the genes upregulated in the invasive tumor cells is Mena, an actin binding protein involved in the regulation of cell motility. There are multiple known splice variants of Mena accounted for by four alternatively included exons, +, ++, +++ and 11a. Using the in vivo invasion assay in rats and mice with mammary tumors we observed that two isoforms of Mena, ++ and +++, are upregulated in the invasive tumor cells and one isoform, 11a, is downregulated. The Mena isoform switching pattern described here may provide a new biomarker for the presence of metastatic cancer cells and for prognosis.

Keywords

Breast cancer Metastasis Biomarker Mena Splice variant